Markers of pre-term labor

Abstract

The invention relates to novel markers of pre-term labor, methods for assessing the status of pre-term labor using the markers, and methods for the diagnosis and therapy of pre-term labor.

1 . A method for detecting one or more pre-term labor marker polypeptide or pre-term labor polynucleotides in a subject comprising: 
 (a) obtaining a sample from a subject;    (b) detecting in polypeptides or polynucleotides extracted from the sample one or more pre-term labor polypeptide or pre-term labor polynucleotide that are associated with pre-term labor; and    (c) comparing the detected amount with an amount detected for a standard.    
     
     
         2 . A method of detecting pre-term labor in a subject, the method comprising comparing: 
 (a) levels of one or more pre-term labor polypeptides or pre-term labor polynucleotides markers that are extracted from a sample from the subject; and    (b) normal levels of expression of the markers in a control sample, wherein a significant difference in levels of markers, relative to the corresponding normal levels, is indicative of pre-term labor.    
     
     
         3 . A method as claimed in  claim 1  or  2  comprising: 
 (a) contacting a biological sample obtained from a subject with one or more binding agent that specifically binds to pre-term labor polypeptide markers or parts thereof; and    (b) detecting in the sample amounts of polypeptides that bind to the binding agents, relative to a predetermined standard or cut-off value, and therefrom determining the presence or absence of pre-term labor in the subject.    
     
     
         4 . A method as claimed in  claim 3  wherein the binding agent is an antibody.  
     
     
         5 . A method for screening a subject for pre-term labor comprising (a) obtaining a biological sample from a subject; (b) detecting in polypeptides extracted from the sample the amount of one or more pre-term labor polypeptide markers; and (c) comparing the amount of markers detected to a predetermined standard, where detection of a level of markers different than that of a standard is indicative of pre-term labor.  
     
     
         6 . A method as claimed in any preceding claim which further comprises detecting multiple pre-term labor polypeptide markers.  
     
     
         7 . A method for determining the presence or absence of one or more pre-term labor marker in a subject comprising detecting one or more pre-term labor polynucleotide in a sample from the subject and relating the detected amount to the presence of pre-term labor.  
     
     
         8 . A method as claimed in  claim 7  wherein the polynucleotide detected is mRNA.  
     
     
         9 . A method of  claim 8  wherein the polynucleotide is detected by 
 (a) contacting the sample with oligonucleotides that hybridize to the polynucleotides; and    (b) detecting in the sample levels of nucleic acids that hybridize to the polynucleotides relative to a predetermined standard or cut-off value, and therefrom determining the presence or absence of pre-term labor in the subject.    
     
     
         10 . A method as claimed in  claim 9  wherein the mRNA is detected using an amplification reaction.  
     
     
         11 . A method as claimed in  claim 10  wherein the amplification reaction is a polymerase chain reaction employing oligonucleotide primers that hybridize to the polynucleotides, or complements of such polynucleotides.  
     
     
         12 . A method as claimed in  claim 9  wherein the mRNA is detected using a hybridization technique employing oligonucleotide probes that hybridize to the polynucleotides or complements thereof, wherein the mRNA is detected by (a) isolating mRNA from the sample and combining the mRNA with reagents to convert it to cDNA; (b) treating the converted cDNA with amplification reaction reagents and primers that hybridize to the polynucleotides, to produce amplification products; (d) analyzing the amplification products to detect an amount of mRNA encoding one or more markers; and (e) comparing the amount of mRNA to an amount detected against a panel of expected values for normal tissue derived using similar primers.  
     
     
         13 . A method for diagnosing and monitoring pre-term labor in a subject comprising isolating polynucleotides in a sample from the subject; and detecting polynucleotides encoding pre-term labor polypeptide markers in the sample wherein the presence of higher or lower levels of polynucleotides encoding pre-term labor polypeptide markers in the sample compared to a standard or control is indicative of pre-term labor.  
     
     
         14 . A method for monitoring the progression of pre-term labor in a subject, the method comprising: (a) detecting in a sample from the subject at a first time point, one or more pre-term labor polypeptide or polynucleotide markers; (b) repeating step (a) at a subsequent point in time; and (c) comparing levels detected in steps (a) and (b), and thereby monitoring the progression of pre-term labor.  
     
     
         15 . A diagnostic composition comprising an agent that binds to a pre-term labor polypeptide marker or hybridizes to a polynucleotide encoding a pre-term labor polypeptide marker.  
     
     
         16 . A method for assessing the potential efficacy of a test agent for preventing, inhibiting, or reducing pre-term labor in a subject, the method comprising comparing: (a) levels of one or more pre-term labor polypeptide or polynucleotide markers, in a first sample obtained from a subject and exposed to the test agent, and (b) levels of the markers in a second sample obtained from the subject, wherein the sample is not exposed to the test agent, wherein a significant difference in the levels of expression of the markers in the first sample, relative to the second sample, is an indication that the test agent is potentially efficacious for preventing, inhibiting or reducing pre-term labor in the subject.  
     
     
         17 . A method of assessing the efficacy of a therapy for preventing, inhibiting, or reducing pre-term labor in a subject, the method comprising comparing: (a) levels of one or more pre-term labor polypeptide or polynucleotide markers in a first sample obtained from the subject; and (b) levels of the markers in a second sample obtained from the subject following therapy, wherein a significant difference in the levels of expression of the markers in the second sample, relative to the first sample, is an indication that the therapy is efficacious for preventing, inhibiting, or reducing pre-term labor in the subject.  
     
     
         18 . A method of selecting an agent for preventing, inhibiting or reducing pre-term labor in a subject the method comprising (a) obtaining a sample containing one or more pre-term labor polypeptide or polynucleotides from the subject; (b) separately exposing aliquots of the sample in the presence of a plurality of test agents; (c) comparing levels of one or more pre-term labor polypeptide or polynucleotide markers in each of the aliquots; and (d) selecting one of the test agents which alters the levels of markers in the aliquot containing that test agent, relative to other test agents.  
     
     
         19 . A method of preventing, inhibiting, or reducing pre-term labor in a subject, the method comprising (a) obtaining a sample containing one or more pre-term labor polypeptide or polynucleotides from the subject; (b) separately maintaining aliquots of the sample in the presence of a plurality of test agents; (c) comparing levels of one or more pre-term labor polypeptide or polynucleotide markers in each of the aliquots; and (d) administering to the subject at least one of the test agents which alters the levels of markers in the aliquot containing that test agent, relative to other test agents.  
     
     
         20 . A method of assessing the potential of a test compound to cause pre-term labor, the method comprising: (a) maintaining separate aliquots of samples containing one or more pre-term labor polypeptide or polynucleotides in the presence and absence of the test compound; and (b) comparing expression of one or more pre-term labor polypeptide or polynucleotide markers, in each of the aliquots, and wherein a significant difference in levels of markers in the aliquot maintained in the presence of the test compound, relative to the aliquot maintained in the absence of the test compound, is an indication that the test compound potentially causes pre-term labor.  
     
     
         21 . A method of any preceding claim wherein the markers are one or more of the polynucleotides or polypeptides encoded by the polynucleotides in Table 2, 3, 4, 5 and/or 6, or SEQ ID Nos. 1 through 232.  
     
     
         22 . A method of any preceding claim wherein the sample is maternal peripheral blood cells, more particularly mononuclear leukocytes.